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Generation of complex bone marrow organoids from human induced pluripotent stem cells
Stephanie Frenz-Wiessner1, Savannah D Fairley1,2, Maximilian Buser3
1Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
Nature Methods
|February 19, 2024
Summary
Researchers developed complex human bone marrow organoids (BMOs) from stem cells. These BMOs mimic the natural bone marrow niche, supporting blood stem cell development and disease modeling.
Area of Science:
- Stem cell biology
- Hematopoiesis research
- Organoid technology
Background:
- The human bone marrow (BM) niche is crucial for lifelong hematopoiesis.
- Existing models do not fully recapitulate the complex BM microenvironment.
Purpose of the Study:
- To develop a method for generating complex human bone marrow organoids (BMOs) from induced pluripotent stem cells (iPSCs).
- To create a physiologically relevant in vitro model for studying hematopoietic development and diseases.
Main Methods:
- Generation of BMOs from human iPSCs.
- Characterization of BMOs using 3D structural analysis and single-cell RNA sequencing.
- Assessment of functional properties including vascularization and stem cell differentiation.
- Xenotransplantation studies in mice.
Main Results:
- BMOs self-organized into 3D structures mimicking the BM microenvironment.
- Organoids exhibited in vivo-like vascular networks and multipotent mesenchymal stem/progenitor cells.
- Single-cell RNA sequencing confirmed a heterocellular composition with hematopoietic stem/progenitor cells (HSPCs) expressing fetal HSC genes.
- BMO-derived HSPCs showed lymphoid potential and transient engraftment capacity.
- BMOs successfully modeled human VPS45 deficiency, an inborn error of hematopoiesis.
Conclusions:
- iPSC-derived BMOs provide a robust in vitro model of the human BM niche.
- BMOs can be used to study hematopoietic development and congenital blood disorders.
- This model offers new avenues for understanding and potentially treating BM diseases.
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